Development of a Numerical Model of High-Intensity Focused Ultrasound Treatment in Mobile and Elastic Organs: Application to a Beating Heart.

High-intensity focused ultrasound (HIFU) is a promising method used to treat cardiac arrhythmias, as it can induce lesions at a distance throughout myocardium thickness. Numerical modeling is commonly used for ultrasound probe development and optimization of HIFU treatment strategies. This study was aimed at describing a numerical method to simulate HIFU thermal ablation in elastic and mobile heart models. The ultrasound pressure field is computed on a 3-D orthonormal grid using the Rayleigh integral method, and the attenuation is calculated step by step between cells. The temperature distribution is obtained by resolution of the bioheat transfer equation on a 3-D non-orthogonally structured curvilinear grid using the finite-volume method. The simulation method is applied on two regions of the heart (atrioventricular node and ventricular apex) to compare the thermal effects of HIFU ablation depending on deformation, motion type and amplitude. The atrioventricular node requires longer sonication than the ventricular apex to reach the same lesion volume. Motion considerably influences treatment duration, lesion shape and distribution in cardiac HIFU treatment. These results emphasize the importance of considering local motion and deformation in numerical studies to define efficient and accurate treatment strategies.

Numerical study of a confocal ultrasonic setup for cavitation creation.

Acoustic cavitation has found a wide range of applications in the last few decades. For potential applications involving cavitation, the acoustic characteristics of a confocal ultrasonic setup are studied: two high-intensity focused ultrasound transducers are mounted so that their focal points overlap. A mathematical simulator is developed that takes into account nonlinear propagation, absorption, and diffraction. Each one of these physical effects is solved in the frequency domain for successive planes. Comparing the confocal setup with equivalent single transducer setups, it is shown that, with the confocal configuration, nonlinear distortion of the waveform is reduced, resulting in a greater peak rarefactional pressure and a lower peak positive pressure. Furthermore, additional features are investigated for confocal configurations such as a greater spatial stability for the focal point, which can be maintained while increasing the pressure level, and a focal region consisting of interference acting as an acoustic trap.

Ultrasound-Guided Transesophageal High-Intensity Focused Ultrasound Cardiac Ablation in a Beating Heart: A Pilot Feasibility Study in Pigs.

Catheter ablation for the treatment of arrhythmia is associated with significant complications and often-repeated procedures. Consequently, a less invasive and more efficient technique is required. Because high-intensity focused ultrasound (HIFU) enables the generation of precise thermal ablations in deep-seated tissues without harming the tissues in the propagation path, it has the potential to be used as a new ablation technique. A system capable of delivering HIFU into the heart by a transesophageal route using ultrasound (US) imaging guidance was developed and tested in vivo in six male pigs. HIFU exposures were performed on atria and ventricles. At the time of autopsy, visual inspection identified thermal lesions in the targeted areas in three of the animals. These lesions were confirmed by histologic analysis (mean size: 5.5 mm(2) × 11 mm(2)). No esophageal thermal injury was observed. One animal presented with bradycardia due to an atrio-ventricular block, which provides real-time confirmation of an interaction between HIFU and the electrical circuits of the heart. Thus, US-guided HIFU has the potential to minimally invasively create myocardial lesions without an intra-cardiac device.

Contribution of inertial cavitation in the enhancement of in vitro transscleral drug delivery.

In ocular drug delivery, the sclera is a promising pathway for administering drugs to both the anterior and posterior segments of the eye. Due to the low permeability of the sclera, however, efficient drug delivery is challenging. In this study, pulsed ultrasound (US) was investigated as a potential method for enhancing drug delivery to the eye through the sclera. The permeability of rabbit scleral tissue to a model drug compound, sodium fluorescein, was measured after US-irradiation at 1.1 MHz using time-averaged acoustic powers of 0.5-5.4 W (6.8-12.8 MPa peak negative pressure), with a fixed duty cycle of 2.5% for two different pulse repetition frequencies of 100 and 1000 Hz. Acoustic cavitation activity was measured during exposures using a passive cavitation detector and was used to quantify the level of bubble activity. A correlation between the amount of cavitation activity and the enhancement of scleral permeability was demonstrated with a significant enhancement in permeability of US exposed samples compared to controls. Transmission electron microscopy showed no evidence of significant alteration in viability of tissue exposed to US exposures. A pulsed US protocol designed to maximum cavitation activity may therefore be a viable method for enhancing drug delivery to the eye.

A multi-element interstitial ultrasound applicator for the thermal therapy of brain tumors.

Interstitial thermal therapy is a minimally invasive treatment modality that has been used clinically for ablating both primary and secondary brain tumors. Here a multi-element interstitial ultrasound applicator is described that allows for increased spatial control during thermal ablation of tumors as compared to existing clinical devices. The device consists of an array of 56 ultrasound elements operating at 6 MHz, oriented on the seven faces of a 3.2 mm flexible catheter. The device was first characterized using the acoustic holography method to examine the functioning of the array. Then experiments were performed to measure heating in tissue-mimicking gel phantoms and ex vivo tissue samples using magnetic resonance imaging-based thermometry. Experimental measurements were compared with results obtained using numerical simulations. Last, simulations were performed to study the feasibility of using the device for thermal ablation in the brain. Experimental results show that the device can be used to induce a temperature rise of greater than 20 °C in ex vivo tissue samples and numerical simulations further demonstrate that tumors with diameters of greater than 30-mm could potentially be treated.

Electronic beam steering used with a toroidal HIFU transducer substantially increases the coagulated volume.

Treatment with high-intensity focused ultrasound is well established but requires extended treatment time. A device composed of 256 elements arranged on a toroidal transducer was developed to increase the coagulated volume. When all the elements are working in phase for 40 s, a volume of 6-8 cm(3) can be ablated. However, the mechanical juxtaposition of single lesions is still necessary for treating one tumor with a diameter of 2 cm. The objective of this study was to combine this toroidal transducer geometry with electronic beam steering to ablate tumors with adequate normal tissue margins and without any mechanical displacement of the high-intensity focused ultrasound device. In vitro tests demonstrated that the coagulated volume obtained from 130 s of total exposure has an average diameter of 41.4 ± 4.0 mm and an average length of 53.3 ± 6.1 mm. This single lesion can be used to treat various size of metastasis, located at depths in the liver ranging 5-45 mm.

Design and evaluation of a transesophageal HIFU probe for ultrasound-guided cardiac ablation: simulation of a HIFU mini-maze procedure and preliminary ex vivo trials.

Atrial fibrillation (AF) is the most frequent cardiac arrhythmia. Left atrial catheter ablation is currently performed to treat this disease. Several energy sources are used, such as radio-frequency or cryotherapy. The main target of this procedure is to isolate the pulmonary veins. However, significant complications caused by the invasive procedure are described, such as stroke, tamponade, and atrioesophageal fistula, and a second intervention is often needed to avoid atrial fibrillation recurrence. For these reasons, a minimally-invasive device allowing performance of more complex treatments is still needed. High-intensity focused ultrasound (HIFU) can cause deep tissue lesions without damaging intervening tissues. Left atrial ultrasound-guided transesophageal HIFU ablation could have the potential to become a new ablation technique. The goal of this study was to design and test a minimally-invasive ultrasound-guided transesophageal HIFU probe under realistic treatment conditions. First, numerical simulations were conducted to determine the probe geometry, and to validate the feasibility of performing an AF treatment using a HIFU mini-maze (HIFUMM) procedure. Then, a prototype was manufactured and characterized. The 18-mm-diameter probe head housing contained a 3-MHz spherical truncated HIFU transducer divided into 8 rings, with a 5-MHz commercial transesophageal echocardiography (TEE) transducer integrated in the center. Finally, ex vivo experiments were performed to test the impact of the esophagus layer between the probe and the tissue to treat, and also the influence of the lungs and the vascularization on lesion formation. First results show that this prototype successfully created ex vivo transmural myocardial lesions under ultrasound guidance, while preserving intervening tissues (such as the esophagus). Ultrasound-guided transesophageal HIFU can be a good candidate for treatment of AF in the future.

Heart ablation using a planar rectangular high intensity ultrasound transducer and MRI guidance.

The aim of this study was to evaluate a flat rectangular (3×10mm(2)) MRI compatible transducer operating at 5MHz. The main task was to explore the feasibility of creating deep lesions in heart at a depth of at least 15mm. The size of thermal necrosis in heart tissue was estimated as a function of power and time using a simulation model. The system was then tested in an excised lamb heart. In this study, we were able to create lesions of 15mm deep with acoustic power of 6W for an exposure of approximately 1min. The contrast to noise ratio (CNR) between lesion and heart tissue was evaluated using fast spin echo (FSE). The CNR value was approximately 22 using T1W FSE. Maximum CNR was achieved with repetition time (TR) between 300 and 800ms. Using T2W FSE, the corresponding CNR was approximately 13 for the 14 in vivo experiments. The average lesion depth was 11.93mm with a standard deviation of 0.62mm. In vivo irradiation conditions were 6W for 60s. The size of the lesion in the other two dimensions was close to 3×10mm(2) (size of the transducer element).

Development of a miniaturized HIFU device for glaucoma treatment with conformal coagulation of the ciliary bodies.

This study examined the feasibility of high-intensity focused ultrasound (HIFU) for glaucoma treatment with conformal coagulation of the ciliary bodies (CB). A miniaturized high frequency (21 MHz) device was developed, based on the geometry of the eye and adapted to the anatomy of the rabbit eyeball. Six line-focus lesions were distributed along a circle and produced by six cylindrical transducers. To be conformal, the numerical model predicted an intensity of 6.9 W/cm(2), with exposure duration of 3 s ON (powered per sector). In vivo experiments were conducted on two rabbits. A significant intraocular pressure reduction was noted (-45% and -31%). Histology demonstrated conformal and homogeneous coagulation of the CB without side effects.

Interstitial thermal ablation with a fast rotating dual-mode transducer.

Interstitial ultrasound applicators can be a minimally invasive alternative for treating targets that are unresectable or are inaccessible by extracorporeal methods. Dual-mode transducers for ultrasound imaging and therapy were developed to address the constraints of a miniaturized applicator and real-time treatment monitoring. We propose an original treatment strategy that combines ultrasound imaging and therapy using a dual-mode transducer rotating at 8 revolutions per second. Real-time B-mode imaging was interrupted to emit high-intensity ultrasound over a selected therapy aperture. A full 360 degrees image was taken every 8th rotation to image the therapy aperture. Numerical simulations were performed to study the effect of rotation on tissue heating, and to study the effect of the treatment sequence on transducer temperature. With the time-averaged transducer surface intensity held at 12 W/cm(2) to maintain transducer temperature below 66 degrees C, higher field intensities and deeper lesions were produced by narrower therapy apertures. A prototype system was built and tested using in vitro samples of porcine liver. Lesions up to 8 mm were produced using a time-averaged transducer surface intensity of 12 W/cm(2) applied for a period of 240 s over a therapy aperture of 40 degrees. Apparent strain imaging of the therapy aperture improved the contrast between treated and spared tissues, which could not be differentiated on B-mode images. With appropriate limits on the transducer output, real-time imaging and deep thermal ablation are feasible and sustainable using a rotating dual-mode transducer.

Sector-switching sonication strategy for accelerated HIFU treatment of prostate cancer: in vitro experimental validation.

The study investigates a new sonication strategy with high-intensity focused ultrasound (HIFU), aiming for improvement of the original Ablatherm procedure in the prostate cancer treatment. The currently implemented and clinically used method (defined as reference) uses a single-element transducer, operated with 60% duty cycle. To implement the novel strategy, the active surface was split into two sectors, which can be powered either sequentially (for temporal switching) or simultaneously (equivalent to a single-element transducer). Numerical simulations were used to predict the lesion shape and to determine for the novel strategy the best set of treatment parameters among the 99 explored cases. The same pattern for the focal point trajectory was executed irrespectively to the sector activating mode. The theoretical duty cycle reached 100% for the sector switching strategy. The HIFU device was built MRI compatible, and consisted of two mirror symmetrical sectors operating at 3 MHz, shaped as a truncated spherical cap. The two sonication strategies were experimentally tested on fresh samples of degassed porcine liver, using fast MR thermometry (proton resonance frequency shift method with voxel size 0.85 x 0.85 x 4.25 mm (3), 2 s/dynamic, 0.5 ( degrees ) C temperature accuracy, two orthogonal slices). A practical value of 87.5% overall duty cycle could be experimentally implemented. The performance of the two sonication strategies was comparatively assessed based on: cumulated thermal dose derived from MR temperature maps, postoperatory MR morphological images sensitive to tissue contrast changes (inversion-recovery T1-weighted turbo spin-echo, voxel size 0.5 x 0.5 x 4 mm (3)) and postoperatory macroscopic tissue examination. Using a sector-switching sonication strategy for prostate cancer treatment-induced lesions of similar size and shape as for the reference approach. When considering the available reserve of duty cycle and the exact lesion size, we concluded the treatment time was reduced by 20% with the new sector switching strategy at equal performance. Further in vivo studies are considered mandatory for preclinical validation.

Gel phantom for use in high-intensity focused ultrasound dosimetry.

An optically transparent phantom was developed for use in high-intensity focused ultrasound (US), or HIFU, dosimetry studies. The phantom is composed of polyacrylamide hydrogel, embedded with bovine serum albumin (BSA) that becomes optically opaque when denatured. Acoustic and optical properties of the phantom were characterized as a function of BSA concentration and temperature. The speed of sound (1544 m/s) and acoustic impedance (1.6 MRayls) were similar to the values in soft tissue. The attenuation coefficient was approximately 8 times lower than that of soft tissues (0.02 Np/cm/MHz for 9% BSA). The nonlinear (B/A) coefficient was similar to the value in water. HIFU lesions were readily seen during formation in the phantom. In US B-mode images, the HIFU lesions were observed as hyperechoic regions only if the cavitation activity was present. The phantom can be used for fast characterization and calibration of US-image guided HIFU devices before animal or clinical studies.

Damping, amplitude, aging tests of stacked transducers for shock wave generation.

New clinical concepts in lithotripsy demand small shock heads. Reducing the size of piezoelectric shock heads will be possible only if the pressure generated at the surface of each transducer can be increased so that the total pressure at the focus remains the same. To solve this problem, different solutions were proposed. For example, it has been demonstrated that piezocomposite material, as opposed to piezoceramic material, allows the generation of a higher surface pressure before breaking, mainly because radial modes are dramatically reduced. In addition, in a previous paper, we showed the feasibility of generating high-pressure pulse waves without increasing the transducer voltage by using sandwiched transducers, which are a stack of two or more transducers. Some discrepancies appeared, however, between the pressure measured at the surface of the front transducer and the arithmetic sum of the pressures generated by each transducer constituting the stack. In fact, development of such stacked transducers capable of generating surface pressures in the range of 2 to 5 MPa is very complex, which may explain why no aging tests have been reported in the literature thus far. In the first part of this paper, we theoretically determine the importance of the electroacoustical coupling between the two transducers on the generated surface pressure. We show that pressure losses due to these electroacoustical couplings are less than 5%. Experimental measurements done on a stacked transducer assembled and tightened in a castor oil-filled tank are in excellent accordance with the theoretical measurements. Using this assembly technique, it was possible to obtain, on average, out of four elements, a pressure of 7.5 MPa for the duration of 4 million shocks, which would allow the treatment of approximately 1000 patients.

Numerical simulation of the electro-acoustical response of a transducer excited by a time-varying electrical circuit.

Existing methods for the modeling of piezoelectric transducer response are generally frequency domain-based. The major disadvantage of this type of model is that they cannot take into account the electrical elements present in the emitting or receiving circuit whose values vary with respect to time. The need for a method that accounts for time-varying elements arises, for example, when the circuit comprises active electrical elements, such as diodes, or when the transducer is excited by capacitive discharge via a switch. Indeed, in this last example, it is known that the output impedance of the generator depends on the state of the switch: if it is off, its value is high; if it is on, its value is low. A time domain-based method is presented to compute the electro-acoustical response of a piezoelectric transducer and its electrical circuit, taking into account the presence of time-varying elements. An application to a current example makes it possible to show the influence of these elements on waveforms and the capacity of our model to account for them.